The present invention provides novel compounds which are pharmacologically useful as thromboxane A.sub.2 antagonist drugs. More specifically, the compounds of the present invention are orally active thromboxane A.sub.2 antagonist agents which promote their effects through their ability to inhibit thromboxane A.sub.2 's powerful induction platelet aggregation and the platelet release reaction. It is thought that the thromboxane A.sub.2 antagonists exhibit their activity by being able to occupy thromboxane receptor sites. In addition to its platelet aggregation action, thromboxane A.sub.2 has been implicated in other potentially noxious actions on various body systems, including bronchoconstriction and pulmonary and systemic vasoconstriction. Thus thromboxane A.sub.2 may be involved in the normal sealing of blood vessels following injury, but in addition may contribute to pathological intravascular clotting or thrombosis. Moreover, the constrictor actions of thromboxane A.sub.2 on bronchiolar, pulmonary vascular and systemic vascular smooth muscle may be important in the development of several anaphylactic conditions, including bronchial asthma. There is also some evidence to implicate thromboxane A.sub.2 in the pathogenesis of inflammation.
Thromboxane A.sub.2 antagonists of the present invention belong to a group of bicycloheptenoic acids as partially exemplified in U.S. Pat. No. 4,596,823 to Jones, et al. The present invention also relates to novel pharmaceutical compositions comprising one or more of the active compounds of the invention in combination with suitable pharmaceutical carriers as well as methods of using such-compounds and pharmaceutical compositions thereof in the treatment, prevention, or mitigation of disease states brought on by the activity of thromboxane A.sub.2. In addition, the compounds can be used in vitro diagnosis (e.g. in assays for thromboxane A.sub.2 and the like).
The invention further relates to novel methods of synthesis of the novel thromboxane A.sub.2 antagonist compounds of the invention, as well as to novel intermediates used in the novel syntheses of the invention.